DOCSLIB.ORG

Biochemistry Citric Acid Cycle As Source of Biosynthetic Precursor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biochemistry Citric Acid Cycle As Source of Biosynthetic Precursor Dr. Vijaya Khader Dr. MC Varadaraj Paper : 04 Metabolism of carbohydrates Module : 12 Citric Acid Cycle as Source of Biosynthetic Precursor 1 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Dr.S.K.Khare,Professor Principal Investigator IIT Delhi. Paper Coordinator Dr. Ramesh Kothari,Professor UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5 Gujarat-INDIA Dr. S. P. SinghProfessor Content Reviewer UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA Dr.Padma Ambalam, Assistant Professor Department of Biotechnology Content Writer Christ College, Affiliated to Saurashtra University, Rajkot-5, Gujarat-INDIA 2 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Description of Module Subject Name Biochemistry Paper Name 04 Metabolism of carbohydrates Module Name/Title 12 Citric Acid Cycle as Source of Biosynthetic Precursor 3 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Citric Acid Cycle as source of Biosynthetic Precursor Objectives 1. To understand the function of a central metabolic pathway that produces precursors and substrates used in biosynthetic processes is the TCA cycle. 2. To examine the importance of citric acid cycle intermediates in the synthesis of amino acids, carbohydrates etc 3. To relate defects inBiogenesis or anabolism, requires substrates to be acted upon that result in the formation of larger more complex molecules. 4. The citric acid cycle is a source of biosynthetic precursors & thus serves as metabolic integration hub. 4 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Introduction The citric acid cycle is involved in both catabolic and anabolic processes, it is known as an amphibole pathway. It is the major degradative pathway for the generation of ATP and its intermediates must be replenished if any are drawn off for biosynthesis. Several intermediates of TCA cycle are used for the synthesis of important compounds, which will have significant cataplerotic effects on the cycle. Acetyl-CoA cannot be transported out of the mitochondria. To obtain cytosolic acetyl- CoA, citrate is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. The oxaloacetate can be used for gluconeogenesis (in the liver), or it can be returned into mitochondria as malate. The carbon skeletons of many non-essential amino acids are made from citric acid cycle intermediates. In this reaction the glutamate is converted into alpha-ketoglutarate, which is a citric acid cycle intermediate. The intermediates that can provide the carbon skeletons for amino acid synthesis are oxaloacetate which forms aspartate and asparagine; and alpha-ketoglutarate which forms glutamine, proline, and arginine (Figure-1). Of these amino acids, aspartate and glutamine are used, together with carbon and nitrogen atoms from other sources, to form the purines that are used as the bases in DNA and RNA, as well as in ATP, AMP, GTP, NAD, FAD and CoA. The pyrimidines are partly assembled from aspartate (derived from oxaloacetate). The pyrimidines, thymine, cytosine and uracil, form the complementary bases to the purine bases in DNA and RNA, and are also components of CTP, UMP, UDP and UTP. The majority of the carbon atoms in the porphyrins come from the citric acid cycle intermediate, Succinyl-CoA. These molecules are an important component of the hemoproteins, such as hemoglobin, myoglobin and various cytochromes.During gluconeogenesis mitochondrial oxaloacetate is reduced to malate which is then transported out of the mitochondria, to be oxidized back to oxaloacetate in the 5 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor cytosol. Figure-1 Overview of Citric Acid Cycle as a source of Biosynthetic Precursor.(Adapted from Garrett and Grisham: Biochemistry 2nd edition). Oxaloacetate is converted to glucose in gluconeogenesis. Succinyl-CoA is a central intermediate in the synthesis of the porphyrins ring of Heme groups, which serve as oxygen carriers (in haemoglobin and myoglobin) and electronCarriers (in cytochromes). And the citrate produced in some organisms is used commercially for a variety of purposes. A Transamination reaction converts glutamate into α -ketoglutarate or vice versa. Glutamate is a precursor for the synthesis of other amino acids and purine nucleotides (Figure-2). Succinyl-CoA is a precursor for porphyrins. Oxaloacetate can be transaminated to form aspartate. Aspartate itself is a precursor for other amino acids and pyrimidine nucleotides. Oxaloacetate is a substrate for gluconeogenesis. 6 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Figure-2 Role of citric acid cycle in anabolism. (Adapted from http://www.up.edu.ps/ocw/repositories/pdf-archive/MGDC2202/body.html) Mechanism of synthesis of Leucine, Alanine and Valine from pyruvate Pyruvate is the end result of glycolysis and can feed into both the TCA cycle and fermentation processes.Reactions beginning with either one or two molecules of pyruvate cause the synthesis of alanine, valine, and leucine. Feedback inhibition of final products is the main method of inhibition, and, in E. coli, the ilvEDA operon also plays a part in this regulation. Valine is produced by a four-enzyme pathway. It begins with the reaction of two pyruvate molecules catalyzed by Acetohydroxy acid synthase yielding α-acetolactate. Step two is the NADPH+ + H+ - dependent reduction of α-acetolactate and migration of the methane groups to produce α, β-dihydroxyisovalerate. This is catalyzed by Acetohydroxyisomer reductase. The third reaction is the dehydration reaction of α, β-dihydroxyisovalerate catalyzed by Dihydroxy acid dehydrase resulting in α-ketoisovalerate. Finally, a transamination catalyzed either by an alanine-valine transaminase or a glutamate-valine transaminase results in valine (Figure-4). The leucine synthesis pathway diverges from the valine pathway beginning with α- ketoisovalerate. α-Isopropyl malate synthase reacts with this substrate and Acetyl 7 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor CoA to produce α-isopropyl malate. An isomerase then isomerizes α-isopropyl malate to β-isopropyl malate. The third step is the NAD+-dependent oxidation of β-isopropyl malate via the action of a dehydrogenase to yield α-ketoisocaproate. Finally is the transamination via the action of a glutamate-leucine transaminase to result in leucine (Figure-4). Figure-3 the biosynthesis of Leu and Val from pyruvate. The action of acetohydroxyacid synthase (AHAS), ketoacid reductoismerase (KARI), and dihydroxyaciddehydratase (DHAD) yields 2-oxoisovalerate that is either transaminated to Val or subjected to additional reactions specific for Leu biosynthesis.(Adapted from Plant Physiology February 2007 vol. 143 no. 2 / 970-986 ) Alanine is produced by the transamination of one molecule of pyruvate using two alternate steps: 1) conversion of glutamate to α-ketoglutarate using a glutamate- alanine transaminase, and 2) conversion of valine to α-ketoisovalerate via Transaminase C. (Figure-4) Not much is known about the regulation of alanine synthesis. The only definite method is the bacterium’s ability to repress Transaminase C activity by either valine or leucine (seeilvEDA operon). Other than that, alanine biosynthesis does not seen to be regulated. 8 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Figure-4 conversion of Pyruvate to Alanine.(Adapted from http://www.namrata.co/subjective-questions-fate-of-pyruvate/) Mechanism of conversion of Acetyl CoA to fatty acids and steroids Acetyl CoA itself is a major biosynthetic precursor for the formation of lipids. Lipogenesis is the process by which acetyl-CoA is converted to fatty acids. Through lipogenesis and subsequent triglyceride synthesis, the energy can be efficiently stored in the form of fats. Lipogenesis encompasses both the process of fatty acid synthesis and triglyceride synthesis (where fatty acids are esterified with glycerol to form fats). The products are secreted from the liver in the form of very-low-density lipoproteins (VLDL). Fatty acids synthesis starts with acetyl-CoA and builds up by the addition of two- carbonunits. The synthesis occurs in the cytoplasm of the cell, in contrast to the degradation (oxidation), (Figure-5) which occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthetase. The major sites of fatty acid synthesis are adipose tissue and the liver. Acetyl-CoA carboxylase Insulin affects ACC in a similar way to PDH. It leads to its dephosphorylation which activates the enzyme. Glucagon has an antagonistic effect and increases phosphorylation, deactivation, thereby inhibiting ACC and slowing fat synthesis.(Figure-5) 9 Metabolism of Carbohydrates Biochemistry Citric Acid Cycle as Source of Biosynthetic Precursor Affecting ACC affects the rate of acetyl-CoA conversion to malonyl-CoA. Increased malonyl-CoA level pushes the equilibrium over to increase production of fatty acids through biosynthesis. Figure-5 Conversion of Acetyl CoA to long chain fatty acids (Adapted from Agronomy 317 - Principles of Weed Science Authored by Dr. Lance R. Gibson Copyright © 2001 Iowa State University.
Load more

Recommended publications
  • Spectroscopy of Porphyrins
    BORIS F. KIM and JOSEPH BOHANDY SPECTROSCOPY OF PORPHYRINS Porphyrins are an important class of compounds that are of interest in molecular biology because of the important roles they play in vital biochemical systems such as biochemical energy conversion in animals, oxygen transport in blood, and photosynthetic energy conversion in plants. We are studying the physical properties of the energy states of porphyrins using the techniques of ex­ perimental and theoretical spectroscopy with the aim of contributing to a basic understanding of their biochemical behavior. INTRODUCTION Metalloporphin Porphyrins are a class of complex organic chemical compounds found in such diverse places as crude oil, plants, and human beings. They are, in most cases, tailored to carry out vital chemical transformations in intricate biochemical or biophysical systems. They are the key constituents of chlorophyll in plants and of hemoglobin in animals. Without them, life would y be impossible. t Free base porphin These molecules display a wide range of chemical and physical properties that depend on the structural details of the particular porphyrin molecule. All por­ ~x phyrins are vividly colored and absorb light in the visible and ultraviolet regions of the spectrum. Some exhibit luminescence, paramagnetism, photoconduc­ tion, or semiconduction. Spme are photosensitizers Wavelength (nanometers) or catalysts. Scientists from several disciplines have been interested in unraveling the principles that cause Fig. 1-The chemical structures for the two forms of por· this diversity of properties. phin are shown on the left. A carbon atom and a hydrogen The simplest compound of all porphyrins is por­ atom are understood to be at each apex not attached to a nitrogen atom.
    [Show full text]
  • ASPP2 Inhibits Tumor Growth by Repressing the Mevalonate Pathway
    Liang et al. Cell Death and Disease (2019) 10:830 https://doi.org/10.1038/s41419-019-2054-7 Cell Death & Disease ARTICLE Open Access ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma Beibei Liang1,RuiChen2, Shaohua Song3,HaoWang4,GuoweiSun5, Hao Yang1,WeiJing6, Xuyu Zhou6,ZhirenFu3, Gang Huang1 and Jian Zhao1 Abstract Cancer is, fundamentally, a disorder of cell growth and proliferation, which requires adequate supplies of energy and nutrients. In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC). Gene expression profile analysis revealed that the expression of key enzymes in the mevalonate pathway were increased when ASPP2 was downregulated. HCC cells gained higher cholesterol levels and enhanced tumor-initiating capability in response to the depletion of ASPP2. Simvastatin, a mevalonate pathway inhibitor, efficiently abrogated ASPP2 depletion-induced anchorage-independent cell proliferation, resistance to chemotherapy drugs in vitro, and tumor growth in xenografted nude mice. Mechanistically, ASPP2 interacts with SREBP-2 in the nucleus and restricts the transcriptional activity of SREBP-2 on its target genes, which include key enzymes involved in the mevalonate pathway. Moreover, clinical data revealed better prognosis in patients with high levels of ASPP2 and low levels of the mevalonate pathway enzyme HMGCR. Our findings provide functional and mechanistic insights into the critical role of ASPP2 in the regulation of the mevalonate pathway and the importance of this pathway in tumor initiation and tumor growth, which may provide a new therapeutic opportunity for HCC.
    [Show full text]
  • Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma Gondii
    H OH metabolites OH Article Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii Joachim Kloehn 1,*,† , Matteo Lunghi 1,†, Emmanuel Varesio 2 , David Dubois 1 and Dominique Soldati-Favre 1,* 1 Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland; [email protected] (M.L.); [email protected] (D.D.) 2 Institute of Pharmaceutical Sciences of Western Switzerland, School of Pharmaceutical Sciences, Mass Spectrometry Core Facility (MZ 2.0), University of Geneva, 1211 Geneva, Switzerland; [email protected] * Correspondence: [email protected] (J.K.); [email protected] (D.S.-F.); Tel.: +41-22-379-57-16 (J.K.); +41-22-379-56-72 (D.S.-F.) † These authors contributed equally to the work. Abstract: Apicomplexan parasites are responsible for devastating diseases, including malaria, toxo- plasmosis, and cryptosporidiosis. Current treatments are limited by emerging resistance to, as well as the high cost and toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on the uptake of many essential metabolites from their host. Toxoplasma gondii, the causative agent of tox- oplasmosis, is auxotrophic for several metabolites, including sugars (e.g., myo-inositol), amino acids (e.g., tyrosine), lipidic compounds and lipid precursors (cholesterol, choline), vitamins, cofactors (thiamine) and others. To date, only few apicomplexan metabolite transporters have been charac- terized and assigned a substrate. Here, we set out to investigate whether untargeted metabolomics can be used to identify the substrate of an uncharacterized transporter. Based on existing genome- Citation: Kloehn, J.; Lunghi, M.; and proteome-wide datasets, we have identified an essential plasma membrane transporter of the Varesio, E.; Dubois, D.; Soldati-Favre, major facilitator superfamily in T.
    [Show full text]
  • Electronic Spectroscopy of Free Base Porphyrins and Metalloporphyrins
    Absorption and Fluorescence Spectroscopy of Tetraphenylporphyrin§ and Metallo-Tetraphenylporphyrin Introduction The word porphyrin is derived from the Greek porphura meaning purple, and all porphyrins are intensely coloured1. Porphyrins comprise an important class of molecules that serve nature in a variety of ways. The Metalloporphyrin ring is found in a variety of important biological system where it is the active component of the system or in some ways intimately connected with the activity of the system. Many of these porphyrins synthesized are the basic structure of biological porphyrins which are the active sites of numerous proteins, whose functions range from oxygen transfer and storage (hemoglobin and myoglobin) to electron transfer (cytochrome c, cytochrome oxidase) to energy conversion (chlorophyll). They also have been proven to be efficient sensitizers and catalyst in a number of chemical and photochemical processes especially photodynamic therapy (PDT). The diversity of their functions is due in part to the variety of metals that bind in the “pocket” of the porphyrin ring system (Fig. 1). Figure 1. Metallated Tetraphenylporphyrin Upon metalation the porphyrin ring system deprotonates, forming a dianionic ligand (Fig. 2). The metal ions behave as Lewis acids, accepting lone pairs of electrons ________________________________ § We all need to thank Jay Stephens for synthesizing the H2TPP 2 from the dianionic porphyrin ligand. Unlike most transition metal complexes, their color is due to absorption(s) within the porphyrin ligand involving the excitation of electrons from π to π* porphyrin ring orbitals. Figure 2. Synthesis of Zn(TPP) The electronic absorption spectrum of a typical porphyrin consists of a strong transition to the second excited state (S0 S2) at about 400 nm (the Soret or B band) and a weak transition to the first excited state (S0 S1) at about 550 nm (the Q band).
    [Show full text]
  • Porphyrins & Bile Pigments
    Bio. 2. ASPU. Lectu.6. Prof. Dr. F. ALQuobaili Porphyrins & Bile Pigments • Biomedical Importance These topics are closely related, because heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma, due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. • Metalloporphyrins & Hemoproteins Are Important in Nature Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methyne (==HC—) bridges. A characteristic property of the porphyrins is the formation of complexes with metal ions bound to the nitrogen atom of the pyrrole rings. Examples are the iron porphyrins such as heme of hemoglobin and the magnesium‐containing porphyrin chlorophyll, the photosynthetic pigment of plants. • Natural Porphyrins Have Substituent Side Chains on the Porphin Nucleus The porphyrins found in nature are compounds in which various side chains are substituted for the eight hydrogen atoms numbered in the porphyrin nucleus. As a simple means of showing these substitutions, Fischer proposed a shorthand formula in which the methyne bridges are omitted and a porphyrin with this type of asymmetric substitution is classified as a type III porphyrin.
    [Show full text]
  • Hydroxy–Methyl Butyrate (HMB) As an Epigenetic Regulator in Muscle
    H OH metabolites OH Communication The Leucine Catabolite and Dietary Supplement β-Hydroxy-β-Methyl Butyrate (HMB) as an Epigenetic Regulator in Muscle Progenitor Cells Virve Cavallucci 1,2,* and Giovambattista Pani 1,2,* 1 Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy 2 Institute of General Pathology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy * Correspondence: [email protected] (V.C.); [email protected] (G.P.) Abstract: β-Hydroxy-β-Methyl Butyrate (HMB) is a natural catabolite of leucine deemed to play a role in amino acid signaling and the maintenance of lean muscle mass. Accordingly, HMB is used as a dietary supplement by sportsmen and has shown some clinical effectiveness in preventing muscle wasting in cancer and chronic lung disease, as well as in age-dependent sarcopenia. However, the molecular cascades underlying these beneficial effects are largely unknown. HMB bears a significant structural similarity with Butyrate and β-Hydroxybutyrate (βHB), two compounds recognized for important epigenetic and histone-marking activities in multiple cell types including muscle cells. We asked whether similar chromatin-modifying actions could be assigned to HMB as well. Exposure of murine C2C12 myoblasts to millimolar concentrations of HMB led to an increase in global histone acetylation, as monitored by anti-acetylated lysine immunoblotting, while preventing myotube differentiation. In these effects, HMB resembled, although with less potency, the histone Citation: Cavallucci, V.; Pani, G. deacetylase (HDAC) inhibitor Sodium Butyrate. However, initial studies did not confirm a direct The Leucine Catabolite and Dietary inhibitory effect of HMB on HDACs in vitro. β-Hydroxybutyrate, a ketone body produced by the Supplement β-Hydroxy-β-Methyl liver during starvation or intense exercise, has a modest effect on histone acetylation of C2C12 Butyrate (HMB) as an Epigenetic Regulator in Muscle Progenitor Cells.
    [Show full text]
  • Of Mevalonate Metabolism'
    ICANCER RESEARCH57. 3498—3505.AugustIS. 9971 Regulation of Proliferation and Ras Localization in Transformed Cells by Products of Mevalonate Metabolism' Jennifer A. Cuthbert2 and Peter E. Lipsky Department of Internal Medicine. The Unit'ersitv of Texas Southwestern Medical (‘enterat Dallas. Dallas. Texas 75235-9151 ABSTRACT position 186, the removal of the three COOH-terminal amino acids at positions 187—189, and carboxymethylation of the new COOH-termi Lovastatin, an inhibitor of 3-hydroxy.3-methylglutaryl (HMG) CoA nab cysteine. In addition, either palmitybation of other cysteine resi reductase, and 6-fluoromevalonate (Fmev), an inhibitor of diphospho dues in the COOH terminus (H-Ras, N-Ras, and K-RasA) or a mevalonate decarboxylase, blocked the synthesis of downstream meval. onate products, including prenyl-derived lipids, and prevented membrane pobybasic domain (K-RasB) is important in enhancing membrane localization of Ras in the myeloid cell line U.937. In contrast to lovastatin, association (7). These processes occur stepwise, and the first step, that which induced cytosol localization of Ras in U-937 cells, Fmev failed to of farnesybation of the full-length polypeptide, is thereby essential for increase cytosolic Ras and also completely prevented the proliferation of plasma membrane localization (12—14).Thus, compounds and muta U.937 cells. Growth of U-937 cells was restored by the addition of lovas tions that block the process of farnesylation interfere with the trans tatin to Fmev-blocked cells. These results implied that a product of formation and proliferation that are dependent upon mutationally mevalonate metabolism proximal to isopentenyl diphosphate was respon. activated Ras.
    [Show full text]
  • Effect of Ph on the Binding of Sodium, Lysine, and Arginine Counterions to L- Undecyl Leucinate Micelles
    Effect of pH on the Binding of Sodium, Lysine, and Arginine Counterions to l- Undecyl Leucinate Micelles Corbin Lewis, Burgoyne H. Hughes, Mariela Vasquez, Alyssa M. Wall, Victoria L. Northrup, Tyler J. Witzleb, Eugene J. Billiot, et al. Journal of Surfactants and Detergents ISSN 1097-3958 Volume 19 Number 6 J Surfact Deterg (2016) 19:1175-1188 DOI 10.1007/s11743-016-1875-y 1 23 Your article is protected by copyright and all rights are held exclusively by AOCS. This e- offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com”. 1 23 Author's personal copy J Surfact Deterg (2016) 19:1175–1188 DOI 10.1007/s11743-016-1875-y ORIGINAL ARTICLE Effect of pH on the Binding of Sodium, Lysine, and Arginine Counterions to L-Undecyl Leucinate Micelles 1 2 1 2 Corbin Lewis • Burgoyne H. Hughes • Mariela Vasquez • Alyssa M. Wall • 2 2 1 3 Victoria L. Northrup • Tyler J. Witzleb • Eugene J. Billiot • Yayin Fang • 1 2 Fereshteh H. Billiot • Kevin F. Morris Received: 20 May 2016 / Accepted: 6 September 2016 / Published online: 20 September 2016 Ó AOCS 2016 Abstract Micelle formation by the amino acid-based sur- surface through both of its amine functional groups.
    [Show full text]
  • 33 34 35 Lipid Synthesis Laptop
    BI/CH 422/622 Liver cytosol ANABOLISM OUTLINE: Photosynthesis Carbohydrate Biosynthesis in Animals Biosynthesis of Fatty Acids and Lipids Fatty Acids Triacylglycerides contrasts Membrane lipids location & transport Glycerophospholipids Synthesis Sphingolipids acetyl-CoA carboxylase Isoprene lipids: fatty acid synthase Ketone Bodies ACP priming 4 steps Cholesterol Control of fatty acid metabolism isoprene synth. ACC Joining Reciprocal control of b-ox Cholesterol Synth. Diversification of fatty acids Fates Eicosanoids Cholesterol esters Bile acids Prostaglandins,Thromboxanes, Steroid Hormones and Leukotrienes Metabolism & transport Control ANABOLISM II: Biosynthesis of Fatty Acids & Lipids Lipid Fat Biosynthesis Catabolism Fatty Acid Fatty Acid Synthesis Degradation Ketone body Utilization Isoprene Biosynthesis 1 Cholesterol and Steroid Biosynthesis mevalonate kinase Mevalonate to Activated Isoprenes • Two phosphates are transferred stepwise from ATP to mevalonate. • A third phosphate from ATP is added at the hydroxyl, followed by decarboxylation and elimination catalyzed by pyrophospho- mevalonate decarboxylase creates a pyrophosphorylated 5-C product: D3-isopentyl pyrophosphate (IPP) (isoprene). • Isomerization to a second isoprene dimethylallylpyrophosphate (DMAPP) gives two activated isoprene IPP compounds that act as precursors for D3-isopentyl pyrophosphate Isopentyl-D-pyrophosphate all of the other lipids in this class isomerase DMAPP Cholesterol and Steroid Biosynthesis mevalonate kinase Mevalonate to Activated Isoprenes • Two phosphates
    [Show full text]
  • Emerging Applications of Porphyrins and Metalloporphyrins in Biomedicine and Diagnostic Magnetic Resonance Imaging
    biosensors Review Emerging Applications of Porphyrins and Metalloporphyrins in Biomedicine and Diagnostic Magnetic Resonance Imaging Muhammad Imran 1,*, Muhammad Ramzan 2,*, Ahmad Kaleem Qureshi 1, Muhammad Azhar Khan 2 and Muhammad Tariq 3 1 Department of Chemistry, Baghdad-Ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; [email protected] 2 Department of Physics, Baghdad-Ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; [email protected] 3 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan; [email protected] * Correspondence: [email protected] (M.I.); [email protected] (M.R.) Received: 26 September 2018; Accepted: 17 October 2018; Published: 19 October 2018 Abstract: In recent years, scientific advancements have constantly increased at a significant rate in the field of biomedical science. Keeping this in view, the application of porphyrins and metalloporphyrins in the field of biomedical science is gaining substantial importance. Porphyrins are the most widely studied tetrapyrrole-based compounds because of their important roles in vital biological processes. The cavity of porphyrins containing four pyrrolic nitrogens is well suited for the binding majority of metal ions to form metalloporphyrins. Porphyrins and metalloporphyrins possess peculiar photochemical, photophysical, and photoredox properties which are tunable through structural modifications. Their beneficial photophysical properties, such as the long wavelength of emission and absorption, high singlet oxygen quantum yield, and low in vivo toxicity, have drawn scientists’ interest to discover new dimensions in the biomedical field. Applications of porphyrins and metalloporphyrins have been pursued in the perspective of contrast agents for magnetic resonance imaging (MRI), photodynamic therapy (PDT) of cancer, bio-imaging, and other biomedical applications.
    [Show full text]
  • Nucleotide Base Coding and Am1ino Acid Replacemients in Proteins* by Emil L
    VOL. 48, 1962 BIOCHEMISTRY: E. L. SAIITH 677 18 Britten, R. J., and R. B. Roberts, Science, 131, 32 (1960). '9 Crestfield, A. M., K. C. Smith, and F. WV. Allen, J. Biol. Chem., 216, 185 (1955). 20 Gamow, G., Nature, 173, 318 (1954). 21 Brenner, S., these PROCEEDINGS, 43, 687 (1957). 22 Nirenberg, M. WV., J. H. Matthaei, and 0. WV. Jones, unpublished data. 23 Crick, F. H. C., L. Barnett, S. Brenner, and R. J. Watts-Tobin, Nature, 192, 1227 (1961). 24 Levene, P. A., and R. S. Tipson, J. Biol. Ch-nn., 111, 313 (1935). 25 Gierer, A., and K. W. Mundry, Nature, 182, 1437 (1958). 2' Tsugita, A., and H. Fraenkel-Conrat, J. Mllot. Biol., in press. 27 Tsugita, A., and H. Fraenkel-Conrat, personal communication. 28 Wittmann, H. G., Naturwissenschaften, 48, 729 (1961). 29 Freese, E., in Structure and Function of Genetic Elements, Brookhaven Symposia in Biology, no. 12 (1959), p. 63. NUCLEOTIDE BASE CODING AND AM1INO ACID REPLACEMIENTS IN PROTEINS* BY EMIL L. SMITHt LABORATORY FOR STUDY OF HEREDITARY AND METABOLIC DISORDERS AND THE DEPARTMENTS OF BIOLOGICAL CHEMISTRY AND MEDICINE, UNIVERSITY OF UTAH COLLEGE OF MEDICINE Communicated by Severo Ochoa, February 14, 1962 The problem of which bases of messenger or template RNA' specify the coding of amino acids in proteins has been largely elucidated by the use of synthetic polyri- bonucleotides.2-7 For these triplet nucleotide compositions (Table 1), it is of in- terest to examine some of the presently known cases of amino acid substitutions in polypeptides or proteins of known structure.
    [Show full text]
  • Construction and Optimization of Mevalonate Pathway for Production Of
    Construction and Optimization of Mevalonate Pathway for Production of Isoprenoids in Escherichia coli by Farnaz Nowroozi A dissertation submitted in partial satisfaction of the requirements for the degree of Joint Doctor of Philosophy with University of California, San Francisco in Engineering-Bioengineering in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Jay D. Keasling, Chair Professor Adam P. Arkin Professor Francis C. Szoka Professor Marc K. Hellerstein Fall 2009 1 The dissertation of Farnaz Foroughi-Boroujeni Nowroozi, titled Construction and Optimization of Mevalonate Pathway for production of Isoprenoids in Escherichia coli , is approved: Chair _______________________________ Date ____________________ _______________________________ Date____________________ _______________________________ Date ____________________ _______________________________ Date ____________________ University of California, Berkeley 2 Abstract Construction and Optimization of Mevalonate Pathway for production of Isoprenoids in Escherichia coli by Farnaz Foroughi-Boroujeni Nowroozi Doctor of Philosophy in Bioengineering University of California, Berkeley Professor Jay D. Keasling, Chair The isoprenoid family, containing over 50,000 members, constitutes one of the most structurally diverse groups of natural products. They range from essential and relatively universal primary metabolites, such as sterols, carotenoids, and hormones, to more unique secondary metabolites that serve roles in plant defense and communication and cellular and organismal development. Although these molecules have vast potential in medicine and industry their production is limited by two factors: 1- The yields from harvest and extraction of these compounds from their native sources are low 2- Due to their complex structure, synthetic routes to most isoprenoids are difficult and inefficient Therefore engineering metabolic pathways for production of large quantities of isoprenoids in a microbial host is an attractive approach.
    [Show full text]